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From the Department of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA.
Address correspondence and reprint requests to Dr. Katzman, Department of Neurosciences (0624), School of Medicine, University of California at San Diego, La Jolla, CA 92093-0949.
The presence of the APOE 
4 allele encoding apolipoprotein E4 (apoE4) is the major genetic risk factor for late-onset Alzheimer's disease (AD). However, the molecular and cellular mechanisms by which APOE 4 renders AD risk are unclear. In this report, we present genetic evidence that an apoE receptor, LRP, may be associated with the expression of late-onset AD. Using a biallelic genetic marker in exon 3 LRP, late-onset AD cases markedly differed from the control subjects in the distribution of LRP genotypes, and this difference was highly accentuated among AD cases with positive family history of senile dementia. Furthermore, the numbers of neuritic plaques were significantly altered as a consequence of different LRP genotypes in postmortem AD cases. Taken together, our results implicate the pathophysiology of LRP in the expression of late-onset AD.
Supported by the National Institutes of Health (AG08205, AG05131) and the Sam and Rose Stein Institute for Research on Aging, UCSD. D.E. Kang was supported by training grant AG00216.
Received October 30, 1996. Accepted in final form December 24, 1996.
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|
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|
|
|
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|
|
|
|
|
|
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|
|
 |
|
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|
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|
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Deceased.